Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352)

Open-label, Randomized Controlled Trial of Hydroxychloroquine, Hydroxychloroquine Plus Azithromycin, Chloroquine Alone, Chloroquine Plus Azithromycin in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection

This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring intensive care unit (ICU) admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate; Drug: Azithromycin; Drug: Chloroquine Sulfate

Detailed Description

This Phase III trial will utilize four treatment strategies in non-critically ill hospitalized participants (not requiring mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin. Investigators are primarily interested in the time to recovery. In addition to study medications there will be daily symptom surveys for 14 days, then weekly thereafter for 4 weeks resulting in a total duration of follow up of 42 days. During hospitalization, daily symptom surveys will be completed in conjunction with the study coordinators. On discharge participants will have the option to complete electronic symptom surveys or complete symptom surveys via telephone with study coordinator. In the event that the participant opts for electronic symptom surveys on discharge participants will in addition receive a follow up call from a study coordination every 7 days during the initial 14 day period. In addition, failure to submit a symptom survey will prompt a study follow up call. Data from standard of care SOC will be collected from medical records.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Infectious Disease Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospitalization for management of SARS CoV-2 infection
• Positive SARS CoV-2 test
• Age >=18 years
• Provision of informed consent
• Electrocardiogram (ECG) ≤48 hours prior to enrollment
• Complete blood count, glucose-6 phosphate-dehydrogenase (G6PD), comprehensive metabolic panel and magnesium ≤48 hours prior to enrollment from standard of care.

• If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study. At least one of the following must be used throughout the study:

  • Condom (male or female) with or without spermicide
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormone-based contraceptive

Exclusion Criteria:

• Contraindication or allergy to chloroquine, hydroxychloroquine or azithromycin
• Current use hydroxychloroquine, chloroquine or azithromycin
• Concurrent use of another investigational agent
• Invasive mechanical ventilation

• Participants who have any severe and/or uncontrolled medical conditions such as:

  • unstable angina pectoris,
  • symptomatic congestive heart failure,
  • myocardial infarction,
  • cardiac arrhythmias or know prolonged QTc >470 males, >480 female on ECG
  • pulmonary insufficiency,
  • epilepsy (interaction with chloroquine),
• Prior retinal eye disease
• Concurrent malignancy requiring chemotherapy
• Known Chronic Kidney disease, eGFR<10 or dialysis

• G-6-PD deficiency, if unknown requires G6PD testing prior to enrollment

  • Known Porphyria
  • Known myasthenia gravis
  • Currently pregnant or planning on getting pregnant while on study
  • Breast feeding
  • AST/ALT >five times the upper limit of normal ULN*
  • Bilirubin >five times the ULN*
  • Magnesium <1.4 mEq/L*
  • Calcium <8.4mg/dL >10.6mg/dL*
  • Potassium <3.3 >5.5 mEg/L*

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hydroxychloroquine alone; Arm 1: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets.	Drug: Hydroxychloroquine Sulfate; anti-rheumatic drug (DMARD); Other Names: HYDROXYCHLOROQUINE Plaquenil
Active Comparator: Hydroxychloroquine plus azithromycin; Arm 2: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets. AND Azithromycin 500mg orally once, followed by 250mg daily for four consecutive days (five days total). The drug will be supplied in 250mg tablets.	Drug: Hydroxychloroquine Sulfate; anti-rheumatic drug (DMARD); Other Names: HYDROXYCHLOROQUINE Plaquenil; Drug: Azithromycin; Antibiotic; Other Names: COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin
Active Comparator: Chloroquine alone; Arm 3: Chloroquine phosphate 1000mg orally once, followed in 12 hours by 500mg, then 500mg orally twice daily for 4 days (Five days in total). The drug will be supplied in 500mg tablets.	Drug: Chloroquine Sulfate; Antimalarial; Other Names: Aralen GENERIC NAME(S): Chloroquine Phosphate
Active Comparator: Chloroquine plus azithromycin; Arm 4: Chloroquine phosphate 1000mg orally once, followed in 12 hours by 500mg, then 500mg orally twice daily for 4 days (Five days in total). The drug will be supplied in 500mg tablets. AND Azithromycin 500mg orally once, followed by 250mg daily for 4 consecutive days (5 days total).The drug will be supplied in 250mg tablets.	Drug: Azithromycin; Antibiotic; Other Names: COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin; Drug: Chloroquine Sulfate; Antimalarial; Other Names: Aralen GENERIC NAME(S): Chloroquine Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hours to Recovery	Time (hours) from randomization to recovery defined as 1) absence of fever, as defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications AND 2) absence of symptoms of greater than mild severity for 24 hours AND 3) not requiring supplemental oxygen beyond pre-COVID baseline AND 4) freedom from mechanical ventilation or death in each Arm/Group,respectively.	42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Fever Resolution	Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications in each Arm/Group,respectively.	42 days

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Jane O'Halloran, MD PhD, Washington University School of Medicine (ID-CRU)

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2020
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: April 4, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Disease Attributes; Coronavirus Infections; Infections; Communicable Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Filaricides; Antinematodal Agents; Anthelmintics; Chloroquine; Chloroquine diphosphate; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: 202003188

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No